Desfesoterodine, (R)-(+)-2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethyl-phenol, having the following formula:
is the active metabolite and the key intermediate in the preparation of tolterodine and fesoterodine. These compounds possess M3—Muscarinic antagonist activity and have been used as a treatment for urinary incontinence and overactive bladder.
Desfesoterodine, as well as certain pharmaceutically acceptable salts thereof, are described in WO2007/138440, U.S. Pat. No. 5,559,269, U.S. Pat. No. 6,809,214 and EP1077912.
WO2010/0130392 describes the tartrate salt of Desfesoterodine.
Different salts and solid state forms of an active pharmaceutical ingredient may possess different properties. Such variations in the properties of different salts may provide a basis for improving formulation, for example, by facilitating better processing or handling characteristics, improving the dissolution profile, or improving stability and shelf-life. These variations in the properties of different salts may also provide improvements to the final dosage form, for instance, if they serve to improve bioavailability. Different salts of an active pharmaceutical ingredient may also give rise to a variety of polymorphs or crystalline forms, which may in turn provide additional opportunities to assess and use variations in the properties and characteristics of a solid active pharmaceutical ingredient.
Polymorphism, the occurrence of different crystal forms, is a property of some molecules and molecular complexes. A single molecule may give rise to a variety of polymorphs having distinct crystal structures and physical properties like melting point, thermal behaviors (e.g. measured by thermogravimetric analysis—“TGA”, or differential scanning calorimetry—“DSC”), X-ray diffraction pattern, infrared absorption fingerprint, raman fingerprint and solid state NMR spectrum. One or more of these techniques may be used to distinguish different polymorphic forms of a compound.
Discovering new salts and solid state forms of a pharmaceutical product can provide materials having desirable processing properties, such as ease of handling, ease of processing, storage stability, ease of purification or as desirable intermediate crystal forms that facilitate conversion to other polymorphic forms. New salts and solid state forms of a pharmaceutically useful compound can also provide an opportunity to improve the performance characteristics of a pharmaceutical product. It enlarges the repertoire of materials that a formulation scientist has available for formulation optimization, for example by providing a product with different properties, e.g., better processing or handling characteristics, or improved shelf-life. For at least these reasons, there is a need for additional salts and solid state forms of Desfesoterodine.